NEW ZEALAND DATA SHEET 1 LARGACTIL 10 MG, 25 MG, 100 MG FILM COATED TABLETS AND 25 MG/ML SOLUTION FOR INJECTION Largactil 10 mg film coated tablets Largactil 25 mg film coated tablets Largactil 100 mg film coated tablets Largactil 25 mg/mL solution for injection 2 QUALITATIVE AND QUANTITATIVE COMPOSITION Tablets: Each tablet contains 10 mg, 25 mg or 100 mg of chlorpromazine hydrochloride Solution for injection contains 25 mg/mL of chlorpromazine hydrochloride. Excipients with known effect: Tablets: Lactose monohydrate Solution for injection: Sodium metabisulfite and sodium sulfite For the full list of excipients, see Section 6.1 List of Excipients. 3 PHARMACEUTICAL FORM Tablets, Solution for injection Tablets 10 mg: white to off-white, circular biconvex, film-coated tablets one face impressed LG10 with the reverse side plain film coated tablet 25 mg: white to off-white, circular biconvex, film-coated tablets one face impressed LG25 with the reverse side plain film coated 100 mg: white to off-white, circular biconvex, film-coated tablets one face impressed LG100 with the reverse side plain film coated Property of the Sanofi group - strictly confidential largactil-ccdsv04-dsv11-17jan20 Page 1 Injection The injection solution is a clear, bright, very pale yellow liquid. 4 CLINICAL PARTICULARS 4.1 THERAPEUTIC INDICATIONS Chlorpromazine is indicated in the following conditions: • Schizophrenia and other psychoses (especially paranoid), mania and hypomania. • In anxiety psychomotor agitation excitement, violent or dangerously impulsive behaviour. Chlorpromazine is used as an adjunct in the short-term management of these conditions. • Intractable hiccup. • Nausea and vomiting of terminal illness (where other medicines have failed or are not available). • Childhood schizophrenia and autism. 4.2 DOSE AND METHOD OF ADMINISTRATION Method of Administration Oral Oral administration should be used whenever possible. Dosages should be low to begin with and gradually increase under close supervision until the optimum dosage within the recommended range for the individual is reached. Individuals vary considerably and the optimum dose may be affected by the formulation used. LARGACTIL tablets should not be crushed and solutions should be handled with care because of the risk of contact dermatitis. The parenteral formulation may be used in emergencies. Intramuscular When given by intramuscular route, chlorpromazine must be administered deep into the muscle. As the solution is an irritant, superficial intramuscular administration should be avoided in order to minimize local reactions. LARGACTIL is too irritant to give subcutaneously. Repeated injections should be avoided if possible. LARGACTIL injection solution has a pH of 5.0 - 6.0 and is incompatible with benzyl-penicillin potassium, pentobarbitone sodium and phenobarbitone sodium. LARGACTIL injection solution, on exposure to light, rapidly develops a pink or yellow colouration; any such solution should be discarded. Property of the Sanofi group - strictly confidential largactil-ccdsv04-dsv11-17jan20 Page 2 Intravenous Infusion When given by intravenous route, chlorpromazine should be administered as an infusion to minimize local reactions. Schizophrenia, Psychoses, Anxiety and Agitation Oral Adult Initially 25 mg three times daily or 75 mg at bedtime increasing by daily amounts of 25 mg to an effective maintenance dose. This is usually in the range 75 to 300 mg daily, but some patients may require up to 1 g daily. Children Under 1 Year: Do not use unless need is life saving. 1-5 Years: 0.5 mg/kg bodyweight every 4 - 6 hours to a maximum recommended dose of 40 mg daily. 6 -12 Years: A third to half the adult dose, to a maximum recommended dose of 75 mg daily. Elderly Start with a third to a half the usual adult dose with a more gradual increase in dosage. Intramuscular Adult For acute relief of symptoms 25 - 50 mg every 6 – 8 hours. Children Under 1 Year: Do not use unless need is life saving. 1-5 Years: 0.5 mg/kg bodyweight every 6 - 8 hours. Dosage is not advised to exceed 40 mg daily. 6-12 Years: 0.5 mg/kg bodyweight every 6 - 8 hours. Not to exceed 75 mg daily. Elderly Doses in the lower range for adults should be sufficient to control symptoms, i.e. 25 mg, 8 hourly. Property of the Sanofi group - strictly confidential largactil-ccdsv04-dsv11-17jan20 Page 3 Intractable Hiccup Oral Adult 25 - 50 mg three or four times daily. Children No information available. Elderly No information available. Intramuscular Adult 25 - 50 mg every 6-8 hours. Children No information available. Elderly No information available Intravenous Infusion Adult If other routes of administration are inappropriate, give 25-50 mg in 500-1000 ml sodium chloride by slow intravenous infusion every 6-8 hours. Children No information available. Elderly No information available. Property of the Sanofi group - strictly confidential largactil-ccdsv04-dsv11-17jan20 Page 4 Nausea and Vomiting of Terminal Illness Oral Adults 10 - 25 mg every 4 - 6 hours. Children Under 1 Year: Do not use unless need is life saving. 1-5 Years: 0.5 mg/kg every 4 - 6 hours. Maximum daily dosage should not exceed 40 mg. 6 - 12 Years: 0.5 mg/kg every 4 - 6 hours. Maximum daily dosage should not exceed 75 mg. Elderly Initially a third to half the adult dose. The physician should then use their clinical judgement to obtain control. Intramuscular Adults 25 mg initially, then 25 - 50 mg every 3 - 4 hours until vomiting stops, then drug to be taken orally. Children Under 1 Year: Do not use unless need is life saving. 1 - 5 Years: 0.5 mg/kg 6 - 8 hourly. It is advised that maximum daily dosage should not exceed 40 mg. 6-12 Years: 0.5 mg/kg every 6 - 8 hours. It is advised that maximum daily dosage should not exceed 75 mg. Elderly For oral use only. Hepatic or Renal Impairment The dosage in these patients may need to be reduced (see Section 4.4 Special Warnings and Precautions for Use). Property of the Sanofi group - strictly confidential largactil-ccdsv04-dsv11-17jan20 Page 5 Elderly or Debilitated The dosage in these patients may need to be reduced (see Section 4.4 Special Warnings and Precautions for Use). 4.3 CONTRAINDICATIONS Chlorpromazine should never be used in the following circumstances: Circulatory collapse. CNS depression, e.g. coma or drug intoxication. Previous history of a hypersensitivity reaction (e.g. jaundice or blood dyscrasia) to phenothiazines, especially chlorpromazine itself, or to any of the excipients contained in the tablets or injection (see Section 6.1 List of Excipients). Bone marrow depression. Phaeochromocytoma. Hepatic failure or active hepatic disease. LARGACTIL Injection contains sodium metabisulfite and sodium sulfite and may cause allergic- type reactions including anaphylactic symptoms and asthmatic episodes in susceptible people. 4.4 SPECIAL WARNINGS AND PRECAUTIONS FOR USE Chlorpromazine generally should not be used in epilepsy, Parkinson’s disease, hypoparathyroidism, myasthenia gravis and prostatic hypertrophy. Epilepsy Chlorpromazine should be avoided in patients with epilepsy as treatment with neuroleptics can result in a lowered seizure threshold. Chlorpromazine may be used in conjunction with anticonvulsant drugs. Parkinson’s Disease Chlorpromazine should be avoided in parkinsonism as phenothiazines may block post synaptic dopamine receptors in the striatum. There is also a possible antagonistic effect of chlorpromazine with dopaminergic agonists used in the treatment of parkinsonism. Property of the Sanofi group - strictly confidential largactil-ccdsv04-dsv11-17jan20 Page 6 Hypoparathyroidism Use of chlorpromazine should be avoided in hypoparathyroidism as a severe dystonic reaction has been reported in patients with untreated hypoparathyroidism. Myasthenia Gravis As the underlying defect in myasthenia gravis is a decrease in the number of available acetylcholine receptors at neuromuscular junctions, chlorpromazine should be avoided in myasthenia gravis due to its strong antimuscarinic effects. Prostate Hypertrophy Chlorpromazine should be avoided in patients with prostate hypertrophy due to the anticholinergic effects of phenothiazines. Antiemetic Effects The antiemetic effects of chlorpromazine may mask signs of overdosage of toxic drugs or obscure the diagnosis of conditions such as intestinal obstruction and brain tumour. Temperature Regulation Phenothiazines depress the mechanism for regulation of temperature. Severe hypothermia may occur during swimming in cold water or in patients receiving antipyretic therapy, and heat stroke may occur in hot weather. Patients who develop pyrexia, along with clouding of consciousness and rigidity should cease medication and undergo immediate investigation, as these are the early symptoms of the neuroleptic malignant syndrome, a potentially lethal adverse effect of major tranquillisers (see Section 4.8 Undesirable Effects). Prolonged Usage As with all phenothiazines, long term usage of chlorpromazine can cause the development of tardive dyskinesia, which may be irreversible (see Section 4.8 Undesirable Effects). Agranulocytosis Agranulocytosis has been reported at an incidence of between 1:1,300 and 1:500,000. Most reported cases have occurred between the fourth and tenth week of treatment. Warn patients to report the sudden appearance of sore throat, fever or other signs of infection. If white blood cell and differential counts indicate cellular depression, stop treatment and start antibiotic and other suitable therapy, subject to the expert guidance of a haematologist.